Screening for Amyloidosis Before Aortic Valve Elective Replacement (SAVER)

Screening for Amyloidosis Before Aortic Valve Elective Replacement (SAVER)

Previous studies detected that up to 15% of patients undergoing aortic valve replacement (AVR) for degenerative aortic stenosis have concomitant transthyretin amyloidosis (ATTR) cardiomyopathy (Castano, 2017). The aim of this study is to investigate the effectivity and practicability of a systematic ATTR-Screening in patients undergoing planned AVR. Moreover, we plan to develop a screening algorithm to detect ATTR in aortic stenosis (AS).

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Valve Stenosis; Amyloidosis
• Intervention / Treatment: Other: The outcome of an intervention is not evaluated, but aortic stenosis and additional amyloidosis are compared.

Detailed Description

Untreated cardiac amyloidosis is accompanied with an impaired prognosis. Amyloidosis is often associated with ventricular hypertrophy which leads to severe heart failure and occurs frequently in conjunction with bradycardic or tachycardic malignant arrhythmia. Patients with degenerative aortic valve stenosis suffer more frequently from cardiac ATTR. However, it remains unclear whether the development of aortic stenosis is promoted by ATTR. Due to very similar symptoms (shortness of breath during physical exertion, reduced walking distance) diagnosis of aortic valve stenosis is more often diagnosed in a typical cohort of patients aged between 70-80 years but, in contrast, leads to underdiagnosis of patients with additional cardiac amyloidosis. Six to fifteen percent of patients with aortic valve replacement due to degenerative aortic valve stenosis exhibit a cardiac amyloidosis. Since cardiac amyloidosis without therapeutic intervention is associated with significantly reduced life expectancy, it can be assumed that these patients will not benefit to the same extent from the AVR alone as patients without ATTR. New therapeutic approaches for patients exhibiting ATTR lead to a reduction of mortality and hospitalizations. The primary aim of this study is to establish a simple ATTR screening tool in patients with planned AVR in the clinical routine and, furthermore, to compare the clinical course following AVR between patients with and without ATTR.

• Study Type: Observational
• Enrollment (Actual): 1000

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients >40 years with aortic valve stenosis who are scheduled to undergo interventional or surgical aortic valve replacement at Deutsches Herzzentrum Berlin or Charité - Universitätsmedizin Berlin during a recruiting period of 18 months; in total approximately 1500 patients.

Description

Inclusion Criteria:

• age ≥40 years
• written informed consent from the patient or of his/her legal guardian
• hospitalization for AVR due to degenerative aortic valve stenosis

Exclusion Criteria:

• hemodynamically unstable patient
• severe co-morbidities with an estimated life expectancy of <1 year

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Aortic valve stenosis undergoing aortic valve replacement; Aortic valve stenosis undergoing aortic valve replacement.	Other: The outcome of an intervention is not evaluated, but aortic stenosis and additional amyloidosis are compared.; We aim to compare patients with aortic valve stenosis with and without cardiac amyloidosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number/ proportion of ATTR cases identified by systematic screening	Enrolment period: 18 months

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Deutsches Herzzentrum Berlin, Klinik für Innere Medizin - Kardiologie; Klinik für Neurologie mit Experimenteller Neurologie, Charité - Universitätsmedizin Berlin

Publications and helpful links

General Publications

• Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T, Drachman BM, Shah SJ, Hanna M, Judge DP, Barsdorf AI, Huber P, Patterson TA, Riley S, Schumacher J, Stewart M, Sultan MB, Rapezzi C; ATTR-ACT Study Investigators. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018 Sep 13;379(11):1007-1016. doi: 10.1056/NEJMoa1805689. Epub 2018 Aug 27.
• Castano A, Narotsky DL, Hamid N, Khalique OK, Morgenstern R, DeLuca A, Rubin J, Chiuzan C, Nazif T, Vahl T, George I, Kodali S, Leon MB, Hahn R, Bokhari S, Maurer MS. Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J. 2017 Oct 7;38(38):2879-2887. doi: 10.1093/eurheartj/ehx350.
• Nitsche C, Aschauer S, Kammerlander AA, Schneider M, Poschner T, Duca F, Binder C, Koschutnik M, Stiftinger J, Goliasch G, Siller-Matula J, Winter MP, Anvari-Pirsch A, Andreas M, Geppert A, Beitzke D, Loewe C, Hacker M, Agis H, Kain R, Lang I, Bonderman D, Hengstenberg C, Mascherbauer J. Light-chain and transthyretin cardiac amyloidosis in severe aortic stenosis: prevalence, screening possibilities, and outcome. Eur J Heart Fail. 2020 Oct;22(10):1852-1862. doi: 10.1002/ejhf.1756. Epub 2020 Feb 20.

Helpful Links

• Amyloidosis center of the Charité

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): March 31, 2023
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: April 28, 2021
• First Submitted That Met QC Criteria: April 28, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: September 30, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Screening; Aortic Stenosis; ATTR; Transthyretin Amyloidosis; Cardiac Amyloidosis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Proteostasis Deficiencies; Aortic Valve Stenosis; Amyloidosis
• Other Study ID Numbers: EA4/235/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No